The two drugs together resulted in greater anti-cancer activity in ATC than either drug alone, says lead researcher Keith Bible, M.D., Ph.D., a Mayo Clinic oncologist.
Anaplastic thyroid cancer is a rare but devastating form of thyroid cancer that typically strikes men and women in their 60s and 70s. It is very aggressive, with a median survival of only about 5 months from time of diagnosis. Only 20 percent of patients survive a year beyond diagnosis, and it has historically been found to be resistant to most therapies.
Pazopanib, a kinase-inhibitor that interferes with the growth of cancer cells, is already approved by the Food and Drug Administration (FDA) to treat renal cancer tumors. Paclitaxel is an FDA-approved chemotherapy drug that disrupts the machinery involved in cell division.
Researchers studied anaplastic thyroid cancer cells and tumors in cell culture and in animal models. Human ATC cells were readily killed, and ATC tumors implanted into mice were 50 percent smaller when treated with the combination in comparison to the response to treatment with either drug alone. Pilot therapy of one patient with metastatic anaplastic thyroid cancer using the combination also resulted in marked tumor shrinkage lasting over six months. "This was a highly unexpected finding for this type of aggressive tumor, which often can double in size in a matter of days," Dr. Bible says.
In previous studies, pazopanib alone was found not effective in the treatment of anaplastic thyroid cancer. Paclitaxel was added to address the aggressiveness of anaplastic thyroid cancer tumors and bolster anti-cancer effects. The team investigated how the two drugs might complement each other.
Monitoring cancer cells multiply in time-lapse video under a microscope, researchers noted that the drug combination resulted in abnormal cell division and an increase in ATC cell death. Although pazopanib had not been known to specifically affect cell division, researchers speculated that the drug might have another unrecognized molecular target within cancer cells.
"We ended up learning that pazopanib also happens to inhibit a protein involved in cell division known as aurora A; this property seems to be involved in producing enhanced effects when pazopanib is combined with paclitaxel," Dr. Bible says. "This finding suggests that the combination may also be useful in treating other cancers, such as breast cancer, in which aurora A is sometimes found to be present in elevated amounts, as it is in ATC," Dr. Bible says.
The results also prompted an ongoing randomized multicenter clinical trial, led by Mayo Clinic and Memorial Sloan-Kettering Cancer Center and administered through the Radiation Therapy Oncology Group, testing the two-drug combination when added to radiation therapy in the initial treatment of patients with anaplastic thyroid cancer.
"This important next step is designed to determine whether the combination of drugs will improve ATC patient survival compared to paclitaxel alone," Dr. Bible says.
The research was funded by National Institutes of Health grants CA125750 and CA13666 and the State of Florida Department of Health Bankhead-Coley Cancer Program. Co-authors include Crescent Isham, Ayoko Bossou, Vivian Negron, Wilma Lingle, Ph.D., Vera Suman, Ph.D. of Mayo Clinic in Rochester, Robert Smallridge, M.D., John Copland, Ph.D., and Laura Marlow of Mayo Clinic in Jacksonville, Fla.; Kelly Fisher and Rakesh Kumar, Ph.D., of GlaxoSmithKline; and Eric Sherman, M.D., of Memorial Sloan-Kettering Cancer Center.
About Mayo Clinic Cancer Center
As a leading institution funded by the National Cancer Institute, Mayo Clinic Cancer Center conducts basic, clinical and population science research, translating discoveries into improved methods for prevention, diagnosis, prognosis and therapy. For information on cancer clinical trials, call 507-538-7623.
About Mayo Clinic
Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit MayoClinic.com or MayoClinic.org/news.
Journalists can become a member of the Mayo Clinic News Network for the latest health, science and research news and access to video, audio, text and graphic elements that can be downloaded or embedded.
Joe Dangor | Source: EurekAlert!
Further information: www.mayo.edu
Further Reports about: anti-cancer effect > ATC > Cancer > cancer cells > cancer tumors > cell division > drug combination > health services > Mayo > Paclitaxel > Sloan-Kettering > Slow Growth > Thyroid > thyroid cancer > Two-Drug
More articles from Health and Medicine:
Dietary amino acids improve sleep problems in mice with traumatic brain injury
12.12.2013 | Oregon Health & Science University
Orbital samples with sight-saving potential
12.12.2013 | NASA/Johnson Space Center
A unique solar panel design made with a new ceramic material points the way to potentially providing sustainable power cheaper, more efficiently, and requiring less manufacturing time.
It also reaches a four-decade-old goal of discovering a bulk photovoltaic material that can harness energy from visible and infrared light, not just ultraviolet light.
Scaling up this new design from its tablet-size prototype to a full-size solar panel would be a large step toward making solar power affordable compared with ...
Atlantische Flohkrebse pflanzen sich jetzt auch in arktischen Gewässern fort
Biologen des Alfred-Wegener-Institutes, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), haben zum ersten Mal nachgewiesen, dass sich in den arktischen Gewässern westlich Spitzbergens auch Flohkrebse aus dem wärmeren Atlantik fortpflanzen.
Diese überraschende Entdeckung deute auf einen möglichen Wandel der arktischen Zooplankton-Gemeinschaft hin, berichten die Wissenschaftler und Wissenschaftlerinnen in der Fachzeitschrift Marine Ecology ...
The molecular architecture of three key proteins and their complexes reveals how plants fine-tune their immune response to pathogens
Plants rarely get sick in their natural environment. When the threat of infection arises, a quick decision is made about the necessary countermeasures. The course is set by a protein which forms complexes with its partner proteins for this purpose.
Jane Parker from the Max Planck Institute for Plant Breeding ...
Researchers studying speciation of butterfly orchids on the Azores have been startled to discover that the answer to a long-debated question "Do the islands support one species or two species?" is actually "three species".
Hochstetter's Butterfly-orchid, newly recognized following application of a battery of scientific techniques and reveling in a complex taxonomic history worthy of Sherlock Holmes, is arguably Europe's rarest orchid species. Under threat in its mountain-top retreat, the orchid urgently requires conservation recognition.
A lavishly illustrated publication, titled "Systematic revision of Platanthera in ...
Researchers from Brown University and the University of Hawaii have found some mineralogical surprises in the Moon's largest impact crater.
Data from the Moon Mineralogy Mapper that flew aboard India's Chandrayaan-1 lunar orbiter shows a diverse mineralogy in the subsurface of the giant South Pole Aitken basin.
The differing mineral signatures could be reflective of the minerals dredged up at the time of the giant impact 4 billion years ago, ...
12.12.2013 | Life Sciences
12.12.2013 | Earth Sciences
12.12.2013 | Studies and Analyses
11.12.2013 | Event News
10.12.2013 | Event News
05.12.2013 | Event News